Intro to Hematology/Oncology and Microcytic Anemia Flashcards
Hematopoiesis is the process of (…) production in adult (…) or in the (…) and/or (…) of the fetus
- blood cell production
- adult bone marrow
- liver
- spleen
- Humans need how many new blood cells per day?
- This continues throughout life to replace blood cells that are lost due to what?
- 100 million
- blood cells growing old and dying, are killed by disease, or are lost through bleeding
Through what process are erythrocytes continiously produced in the red bone marrow of large bones, at a rate of about 2 million per second in a healthy adult?
erythropoiesis
- In adults, (…) is the site of red blood cell production (erythropoiesis)
- In the embryo, (…) is the main site of red blood cell production (erythropoiesis)
- red bone marrow
- the liver
- Erythropoiesis (production of RBC) is stimulated by (…)
- What is this synthesized by?
- Just before and after leaving the bone marrow, the young, developing cells are known as (…); these comprise about (…)% of circulating RBCs
- When these red blood cells are matured, in a healthy individual, these cells live in blood circulation for about (…) days in an adult, and (…) days in a full term infant
- At the end of their lifespan, RBCs are removed from circulation through the (…)
- the hormone erythropoietin (EPO)
- kidney
- reticulocytes; 1%
- 100-120 days; 80-90 days
- spleen
How much oxygen can hemoglobin carry?
1200 million oxygen molecules
What can you order if someone is bleeding in between where scopes cannot reach?
- imaging (CT)
- angiogram
- pill endoscopy
- What is the normal platelet count?
- Is a platelet a cell? If not, what is it?
- 150-450 platelets per microliter of blood
- no, it is a fragment
- What percentage of RBCs are productive vs stored?
- What percentage of WBCs are productive vs stored?
- What percentage of thrombocytes are productive vs stored?
- 100% productive, 0% stored
- 50% productive, 50% stored
- 70% productive, 30% stored
- Bone marrow is confined to cavity of (…)
- It is the primary site of residence of (…) cells
- It is also called (…) tissue
- What are the two types of bone marrow?
- What do each types of the bone marrow produce?
- bones
- hematopoietic stem cells
- myeloid tissue
- red and yellow bone marrow
- red bone marrow: WBCs, RBCs, platelets; yellow bone marrow: cartilage, fat, or bone cells
Where can you find adult active bone marrow?
- pelvic bones
- vertebrae
- cranium and mandible
- sternum and ribs
- humerus
- femur
- What stem cells proliferate and differentiate under the control of a variety of cytokines and growth factors in blood cells?
- What stem cells continue to have unlimited differentiation potential and can grow into different kinds of tissues?
- What stem cells are more limited but have abilities to differentiation into many different types of cells?
- hematopoietic stem cells
- pluripotent stem cells
- multipotent stem cells
What stimulates progenitor cells (from hematopoietic stem cells) to mature and can be used to increase neutrophils?
colony-stimulating factors (CSFs) or hematopoietic growth factors
What do hematopoietic stem cells form?
progenitor cells
- What is the development of RBCs?
- Erythrocytes are derived from (…)
- Maturation of RBCs are stimulated by (…) which is secreted by (…) in response to tissue (…)
- erythropoiesis
- erythroblasts (normoblasts)
- erythropoietin; secreted by kidneys; tissue hypoxia
Describe what a reticulocyte count is and what it indicates?
- count of immature erythrocytes
- index of erythropoietic activity
- indicates whether new RBCs are being produced
In each step of erythropoiesis, the quantity of hemoglobin (…) and the nucleus (…) in size
- increases
- decreases
Why is EPO secreted by the kidneys in response to tissue hypoxia?
because you want to be able to carry more oxygen in your body, so stimulating secretion of RBCs means you will have more cells carrying oxygen
Describe the formation of RBCs from the stem cell to the erythrocyte
- hematopoietic stem cell (hemocytoblast)
- proerythroblast (committed cell)
- basophilic erythroblast (phase I→ribosome synthesis)
- polychromatic erythroblast (phase II→hemoglobin accumulation)
- orthochromatic erythroblast (phase II→hemoglobin accumulation)
- reticulocyte (phase 3→ejection of nucleus)
- erythrocyte
- Numbers of circulating RBCs in healthy individuals remain (…)
- (…) cells of the kidney produce erythropoietin
- (…) stimulates the production and release of erythropoietin
- Erythropoietin causes an increase in (…) and release from the (…)
- constant
- peritubular cells
- hypoxia
- RBC production; bone marrow
(…) cells sense the blood and oxygen level in the kidneys which then stimulates the release of EPO and production of RBC if blood/oxygen level gets too low
juxtaglomerular cells
What are some different things that can cause hypoxia?
(five things)
- decreased RBCs
- decreased hemoglobin synthesis
- decreased blood flow
- hemorrhage
- increased O2 consumption by tissues
What is the name of the process for production of WBCs?
leukopoiesis
- Production of WBCs are stimulated by two types of chemical messengers from (…) and (…)
- What are the names of these chemical messengers?
- red bone marrow and mature WBCs
- interleukins and colony stimulating factors (CSFs) which are named for the type of WBC they stimulate (granulocyte-CSF stimulates granulocytes)
- All leukocytes originate from (…) stem cells which branches into 2 pathways
- What are these two pathways?
- hemocytoblast stem cells
pathways: - lymphoid stem cells produces lymphocytes
- myeloid stem cells produce all other elements
The two pathways of hemocytoblast stem cells is important to discuss when it comes to (…) because you can have acute/chronic lymphoid (…) and acute/chronic myeloid (…)
all leukemia
What committed cells do lymphoid cells differentiate into?
- B lymphocyte precursor
- T lymphocyte precursor
- What do B cells make?
- When stimulated, B cells transform to (…)
- antibodies
- plasma cells
- What is the name of the process that describes formation of platelets?
- What happens when platelets get too high?
- What happens when platelets get too low?
- thrombopoiesis
- too much clotting
- excessive bleeding
What percentage of blood composition makes up the cellular components (RBCs → hematocrit)?
45%
- What is blood plasma made up of?
- What transports ions, hormones, lipids, aids in immune function, and helps form hemoglobin?
- plasma proteins, other solutes, water
- globulins
- What is the function of erythrocytes?
- What is the function of neutrophils (WBC → grandulocytes)?
- What is the function of eosinophils (WBC → granulocytes)?
- What is the function of basophils (WBCs → granulocytes)?
- transports oxygen and carbon dioxide
- phagocytize bacteria
- kill parasitic worms; complex role in allergy and asthma
- release histamine and other mediators of inflammation; contain heparin (anticoagulant)
- What is the function of lymphocytes (WBCs)?
- What is the function of monocytes (WBCs)?
- What is the function of platelets?
- mount immune response by direct cell attack or via antibodies
- phagocytosis; develop into macrophages in the tissues
- seal small tears in blood vessels; instrumental in blood clotting
Platelets are the (…) step in the clotting cascade
second step
In a blood smear, if there are many basophils, what could this indicate?
leukemia
Label
What are the main general indications for peripheral blood smears?
- can verify automated instrument
- can provide a potential immediate specific diagnosis (ex: leukemia)
- can narrow differential diagnostic list
When receiving an abnormal platelet count, what two things should you think to ask yourself?
- What was the previous/baseline platelet count
- Were the platelets possibly clumping in the test tube
What are the clinical features that suggest ordering a peripheral blood smear?
(there’s 8)
- lymphodenopathy or splenomegaly
- clinically evident anemia
- brusing/bleeding tendency
- acute renal failure
- jaundice/hypertension in a pregnant female (preeclampsia)
- bone pain
- unexplained chest/abdominal pain OR acute splenic enlargment in a child
- unexplained hyperbilirubinemia
What test can you use to also look at the size/shape of blood cells/fragments?
peripheral blood smear
What are different alterations you can have in erythrocytes?
- too many cells (polycythemias)
- too few cells (anemias)
- normal number of cells with abnormal components
What is a reduction in the total number of erythrocytes in the circulating blood or the quality or quanity of hemoglobin?
anemia
What can lead to anemia (what causes it)?
- impaired erythrocyte production (not making enough)
- acute or chronic blood loss (losing them)
- increased erythrocyte destruction (destroying them)
- combination of the above
What are the different classifications for anemia?
- etiologic factor (pathophysiologic cause) → ex: due to peripheral destruction, abnormal globin synthesis, etc.
- size → ends in “-cytic”; macro, micro, normocytic
- hemoglobin content → ends in “-chromic”; normo, hypochromic
What are the different pathophysiologic classifications and what is included in each?
- decreased RBC production
**hemoglobin synthesis
**DNA synthesis
**stem cell
**bone marrow infiltration
**pure red cell aplasia - increased RBC destruction
**instrinsic hemolysis
**extrinsic hemolysis - blood loss
What disorders can cause hemoglobin synthesis issues leading to decreased RBC production?
- iron deficiency
- thalassemia
- anemia of chronic disease
What disorders can lead to DNA synthesis issues leading to decreased RBC production?
- megaloblastic anemia
What stem cell disorders can lead to decreased RBC production?
- aplastic anemia
- myeloproliferative leukemia
What bone marrow infiltration disorders can cause decreased RBC production?
- carcinoma
- lymphoma
- Describe what happens in intrinsic hemolysis
- What disorders can cause intrinsic hemolysis leading to increased RBC destruction?
problems with the RBC itself that makes it die earlier
- hereditary spherocytosis
- elliptocytosis
- sickle cell
- unstable hemoglobin
- G6PD deficiency
- Describe what happens in extrinsic hemolysis
- What disorders cause extrinsic hemolysis leading to increased RBC destruction?
nothing wrong with RBC, it just starts getting attacked
- warm and cold antibody
- TTP-HUS
- mechanical cardiac valve
- infections
- hyperspenism
- What is MCV (mean corpuscular volume) of erythrocytes describing?
- What is the norman MCV value?
- the difference in RBC size
- 80-100
- What are the different disorders/diseases that can cause microcytosis anemia (small RBC size)?
- Which ones are the most common?
- iron deficiency
- thalassemias
- anemia of chronic disease
- sideroblastic anemia (aquired: anti TB drugs; congenital)
iron deficiency and anemia of chronic disease are most common
- What are some causes for macrocytic anemia (large RBC size)?
- What are the two most common reasons for macrocytic anemia?
- RBC aplasia
- alcoholism
- aplastic anemia
- myelodysplastic syndromes
- megaloblastic anemias (B12, folic acid deficiency)
- hemolytic anemias (can be macro or normocytic)
megaloblastic anemias and hemolytic anemias
What are the two types of hemolytic anemias? Describe them (what may cause them).
- extrinsic → antibody mediated, microangiopathic hemolytic, toxins, malaria
- intrinsic → RBC membrane defects, hemoglobinopathies, enzymopathies
What conditions can lead to normocytic anemia (normal size RBCs)?
- anemia of chronic disease (when it gets really bad → microcytic)
- acute hemorrhage
- hemoglobinopathies
- primary bone marrow failure (decreased erythroid progenitors)
- secondary to chronic disease
- sickle cell anemia (if not having episode, may appear normal)
What are types of primary bone marrow failure may lead to normocytic anemia?
- aplasia
- myelophthisis
What describes the replacement of hematopoietic tissue in the bone marrow by abnormal tissue, usually fibrous tissue or malignant tumors that are most commonly metastatic carcinomas?
myelophthisis
- What is it called when RBCs are present in various sizes?
- What is it called when RBCs are present in various shapes?
- anisocytosis
- poikilocytosis
Label
- This arrow is indicating (…) which is defined as the presence of erythrocytes with a blue tinge to their cytoplasm.
- This indicates a (…) cell was recently released from the bone marrow and is due to the presence of (…)
- polychromasia
- young cell
- RNA
- In this blood smear, (…) can be defined as a cell with a diameter less than that of the nucleus of a normal small lymphocyte
- There are also some cells showing (…), an area of central pallor larger than one third of the diameter of the red cell
- mycrocytic RBC
- hypochromia
- This is demonstrating a (…) which has a diameter that is greater than the nucleus of a small lymphocyte
- This smear also has (…) in which the cells are larger and more oval in shape (arrow)
- This is important as it is a characteristic of (…) anemia
- macrocyte
- oval macrocytes
- megaloblastic anemia
- This smear is showing a (…) which is a red cell lacking central pallor because of its shape
- In (…), there are usually cells in which the central pallor is reduced rather than absent
- spherocyte
- hereditary spherocytosis
This smear is showing (…) which is an erythrocyte with a hemoglobinized area in the middle of the normal area of central pallor
target cell
- This smear is showing (…)
- These cells are seen in what condition(s)?
- sickle cells
- sickle cell anemia, sickle cell/hemoglobin C disease, sickle cell/beta-thalassemia
- This smear is showing (…) which are defined as fragments of erythrocytes
- Some of these are referred to as (…) because of their typical shape
- These are seen in what conditions?
- schistocytes
- helmet cells
- microangiopathic hemolytic anemias, mechanical hemolysis
- This smear is showing (…)
- When these are seen in these numbers, they are indicative of (…)
- Smaller numbers are seen in other conditions such as (…) where they may be referred to as (…)
- elliptocytes
- hereditary elliptocytosis
- iron deficiency anemia
- pencil cells
- This smear is showing (…)
- These are a characteristic of (…) but are are seen in what other conditions?
- teardrop poikilocytes
- primary myelofibrosis
- myelofibrosis secondary to bone marrow infiltration and megaloblastic anemia
- This smear is showing (…) which is a cell that appears to have a central mouth-shaped or slit-like stoma
- Less common causes of this is (…)
- More common causes of this include (…)
- stomatocyte
- hereditary stomatocytosis
- alcohol and hydroxycardamide therapy
- This smear is showing (…) is is an iron-containing red cell inclusion
- These are seen following (…), (…) and (…)
- pappenheimer bodies
- splectomy, other hyposplenic states, and sideroblastic anemias
- This smear is showing (…) meaning there are fine, coarse purplish blue dots dispersed through the red cell
- These are very nonspecific features in thalassemia, lead poisoning, etc.
basophilic stippling
- This smear is showing (…) which are stacks of red cells
- These result in an increase of high-molecular weight globulins in the plasma
- rouleaux formation
- This smear is showing (…) which are irregular aggregates of red cells
- This is seen in mycoplasma pneumoniae infections and others such as mono and chronic cold hemagglutinin disease
red cell agglutinates
What blood smear feature is found in these conditions:
- hereditary spherocytosis
- autoimmune hemolytic anemia
- drug-induced immune hemolytic anemia
- Clostridium perfringens sepsis
spherocytes
What blood smear feature is found in these conditions:
- hereditary elliptocytosis
elliptocytes
What blood smear feature is found in these conditions:
- G6PD deficiency
- oxidant damage from chemixals/drugs in individuals with normal red cell enzymes
- liver failure d/t Wilson disease (unstable release of copper from liver)
- unstable hemoglobin
- hemoglobin C homozygosity
irregularly contracted cells
What blood smear features are found in these conditions:
- sickle cell disease
sickle cells and boat shaped cells
What blood smear features are found in these conditions:
- hemoglobin C homozygosity
- other hemoglobinopathies
- hereditary xerocytosis
target cells
What blood smear feature is found in these conditions:
- hereditary stomatocytosis
stomatocytes
What blood smear feature is found in these conditions:
- liver failure (spur cell hemolytic anemia)
acanthocytes
What blood smear feature is found in these conditions:
- lead poisoining
- pyrimidine 5’ nucleotidase deficiency
basophilic stippling
What blood smear features is found in these conditions:
- microangiopathic hemolytic anemia
- mechanical hemolytic anemia
red cell fragments (schistocytes)
RBCs should be smaller than what?
WBCs
- If you receive a low H&H, what should you look at next?
- If Hg comes back high, what does that mean?
- look at MCV and then MCHC
- too much blood
- What is the normal hemoglobin value for M/F?
- What is the normal hematocrit value for M/F?
- What is the normal RBC value for M/F?
- What is the normal MCV value?
- What is the normal reticulocyte count value?
- M: 13.5-17.5; F:12-16
- M: 40-52; F: 36-48
- M: 4.5-6.0 F: 4.0-5.4
- 81-99 (anything below 75 is low)
- 20,000-100,000
What is the normal WBC count?
4.5-11
Why would these WBCs be elevated:
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
- bacterial infections
- viral infections
- chronic infections (TB)
- parasites
- bee stings; allergic
What would cause low WBCs (think chronic)?
- autoimmune
- lupus - leukemia
- aplastic anemia
- chemotherapy
What would cause elevated platelets?
chronic cancer
What causes low platelets?
- sepsis
- bleeding
- liver disease
- cancer
What can cause low hemoglobin and hematocrit?
- chronic kidney disease
- anemia
- cancer leukemia
What are some anemia symptoms and signs?
- often no symptoms
- fatigue, dyspnea, dizziness
- palpitations, rapid heart rate
- pallor, coldness, sweating
- decreased exercise tolerance
- changed stool color
- spleen enlargement
In anemia, if Hg < 7.5, what increases?
CO, SV, HR
What are the severe symptoms of anemia?
- cardiac-dizziness, HA, syncope, tinnitus, vertigo
- irritable, decreased sleep and concentration
- cold sensitivity
- GI: indigestion, anorexia, nausea
- females: abnormal menstrutation, amenorrhea, increased bleeding
- males: impotence, loss of libido
- Usually the symptoms of anemia are (…)
- If a patient complains of breathing issues, don’t always assume its their (…) that are the issue
- progressive
- lungs
- Etiologic events such as decrease in erythropoiesis (blood loss) or an increase in RBC destruction can lead to a (…) in RBC and hemoglobin
- This, as a result, (…) the oxygen carrying capacity leading to tissue (…)
- What are some of the compensatory mechanisms of this?
- decrease
- decreases
- tissue hypoxia
- increase oxygen demands for work of heart, cardiovascular (increase HR/SV, capillary dilation), renal, extracellular fluid, etc
In anemia, one of the compensatory mechanisms of tissue hypoxemia is an increase in SV, this can increase the work load of the heart and can cause events such as (…) and (…)
- heart murmers
- high-output cardiac failure
In the assessment of anemia, you must first determine is the anemia is from (…) or (…) or (…)
- decreased production
- loss of blood cells from hemorrhage or hemolysis
What are the characteristics of anemia due to decreased red cell production?
- usually acquired
- onset is insidious
- reticulocyte count is inappropriately low
- red cell indices (MCV, MCHC) are informative
- bone marrow examination is often required for diagnosis
What are the characteristics of anemia caused by an increased red cell destruction (hemolysis)?
- often inherited
- onset may be abrupt or insidious
- reticulocyte count is increased
- red cell morphology on peripheral blood smear is usually informative
- bone marrow examination is usually not indicated
Anemia caused by (…) must be ruled out in any patient with anemia (ruled out ASAP)
blood loss
Pertaining to anemia due to acute blood loss:
- symptoms secondary to (…) and (…)
- vital signs reflect (…) compensation
- blood loss in excess of 1500 ml usually leads to (…)
- Not an initial decrease in (…) or (…) levels
- Theres an increase in (…) and (…) in WBCs
- First few days after loss, (…) increase from hypoxic trigger to bone marrow
- (…) will increase initially since young RBCs are larger than old ones
- hypovolemia and hypoxia
- CV compensation
- cardiovascular collapse
- Hgb or Hct levels
- leukocytosis and left shift in WBCs
- retics increase
- MCV
What should you assess when looking at anemia due to acute blood loss?
postural signs: when lifted from supine to sitting, an increase in pulse of 25% or more or a fall in the systolic BP of 20 mmHg or more signifies hypovolemia
- Prompt assessment and treatment is critical in anemia due to (…) blood loss
- What does treatment of this include?
- acute blood loss
treatment: - transfusion of PRBCs, central monitoring of volume replacement
- control sites of bleeding
- emergent coagulation profile
What is the normal blood volume amount in M/F?
males: 6L
females: 5L
Pertaining to anemia due to chronic blood loss:
- usually due to lesions in the (…) or (…)
- test stool specimens for (…)
- manifestations is that of (…) anemia
- GI tract or uterus
- occult blood
- iron deficiency anemia
- When assessing anemia due to chronic blood loss, testing stool samples for occult blood is essential but often (…)
- You may need to check (…) specimens over a prolonged period of time as GI bleeding may be (…)
- overlooked
- serial specimens
- intermittent
What does the anemia work-up consist of?
- CBC (results of Hgb/Hct and RBC indices drives rest of work up; depends on acuity and severity; MCV: micro vs macro)
- reticulocyte count (distinuishes decreased production from hemolysis)
- peripheral blood spear (especially in unexplained anemia
- What distinguishes anemia caused by decreased RBC production from hemolysis?
- A significant elevation of this is suggestive of what?
- An inappropriately low count suggests what?
- reticulocyte count
- hemolysis
- failure to produce RBCs
What are possible parts of anemia work-ups?
- ferritin level
- TIBC (total iron binding capacity)
- transferrin saturation
- serum iron
- haptoglobin, LDH, and bilirubin level (if suspecting hemolysis)
- Hgb electrophoresis (if suspecting sickle cell and thalassemia)
- erythropoietin level
- if macrocytic, B12, folic acid, and homocysteine/methylmalonic acid
- bone marrow examination
Which 3 tests should you order if a patient has microcytic anemia?
- ferritin level
- TIBC
- transferrin saturation
If suspecting hemolytic anemia, what test(s) can you order?
- haptoglobin
- LDH
- bilirubin levels
If suspecting sickle cell and thalassemia, what should you order?
Hgb electrophoresis
Pertaining to bone marrow examination of anemia work-up:
- Assessing quantiy and quality of (…) for a defect in cell production due to (…) or (…)
- Determines overall (…). Ratio of myeloid to (…)
**may be increased by inclusion of (…)
**increases in (…), (…), or (….) pf myeloid cells
- Also evaluates presence of cellular infiltrates as in (…), (…), or (…)
- RBC precursors; hypoplasia or ineffective erythropoiesis
- cellularity; erythroid precursors
- circulating leukocytes
- infection, leukemoid reaction, or neoplastic proliferation of myeloid cells
- leukemia, lymphoma, or multiple myeloma
What are characterized by RBCs that are abnormally small and contain reduced amounts of hemoglobin?
microcytic-hypochromic anemias
What are causes of microcytic-hypochromic anemias?
- disorders of iron metabolism
- disorders of porphyrin and heme synthesis
- disorders of globin synthesis
What is the differential diagnosis of microcytosis (microcytic-hypochromic anemia) in children and adolescents?
- iron deficiency anemia
- thalassemia trait
- other hemoglobinopathies
- lead toxicity
- chronic inflammation
- sideroblastic anemia
What is the differential diagnosis of microcytosis (microcytic-hypochromic anemia) for menstruating women?
- iron deficiency anemia
- thalassemia trait
- pregnancy
- anemia of chronic disease
- sideroblastic anemia
What is the differential diagnosis of microcytosis (microcytic-hypochromic anemia) in men and nonmenstruating women?
- iron deficiency anemia
- anemia of chronic disease
- unexplained anemia
- thalassemia trait
What type of anemias this describe:
- improper Hgb making cells smaller, MCV < 80 fL
microcytic-hypochromic anemias
What main conditions are microcytic-hypochromic anemias?
(TICS)
- Thalassemias
- Iron deficiency
- Chronic disease/inflammatory
- Sideroblastic
- Any pathology that leads to less iron being taken up by precursor RBCs is going to produce (…) and (…) cells
- What tests can be helpful in diagnosing this type of anemia?
- smaller (microcytic) and less red (hypochromic) cells
- Iron, TIBC, serum ferritin, transferrin
Describe the characteristics of microcytic-hypochromic anemia caused by chronic disease/inflammation
- inflammation can be detected with CRP or ESR
- 30% microcytic, 70% normocytic (d/t damage to kidneys)
- normal or elevated ferritin with elevated transferrin saturation typical
Describe the characteristics of microcytic-hypochromic anemia caused by thalassemia?
- aided by hemoglobin electrophoresis
- quantifies Hgb A2 and F
Describe the characteristics of microcytic-hypochromic anemia caused by sideroblastic anemia?
can be inherited or acquired
What should the first test be thats ordered if someone has microcytic anemia? What does this determine and why?
- ferritin (stores iron)
- makes sure they don’t have any chronic inflammation because it is an APR
What is the likely condition if ferritin is low (< 30 ng/mL)?
IDA
What is the likely/suspected condition(s) if ferritin is high (>30 ng/mL)?
- suspected IDA
- suspected ACD
- thalassemia
What are these levels in iron deficiency anemia:
- serum iron
- TIBC
- serum ferritin
- low serum iron
- high TIBC
- low (<30 μg/L) serum transferrin
What are these levels in anemia of chronic disease:
- serum iron
- TIBC
- serum ferritin
- low serum iron
- normal or low TIBC
- normal or high serum ferritin
What are these levels in sideroblastic anemia:
- serum iron
- TIBC
- serum ferritin
- high serum iron
- normal TIBC
- high serum ferritin
- What is the most common type of anemia worldwide?
- Which individuals are at the highest risk for this type of anemia?
- What is this type of anemia associated with in children?
- iron deficiency anemia
- older adults, women, infants, those living in poverty
- cognitive impairments
What are some causes of iron-deficiency anemia?
- inadequate dietary intake
- excessive blood loss
- chronic parasitic infestations
- metabolic or functional iron deficiency
- menorrhagia (excessive bleeding during menstruation)
What are the top 2 causes of iron-deficiency anemia in the US?
- excessive blood loss
- menorrhagia
What is this describing:
- significant reduction in the mass of circulating RBCs
- insufficient amounts of iron = body cannot produce enough hemoglobin that enables RBCs to carry O2
iron deficiency anemia
Pertaining to iron-deficiency anemia:
- most common form of (…) worldwide
- 1.6 billion worldwide are anemic, with (…)% being iron-deficiency
- (…)% of US adolescent females have iron levels low enough to cause anemia
**common in menstruating women due to (…)
**(…) increases chances due to demand increases
- Rates are higher in (…) and (…) due to nutritional deficiencies
- (…)% of adult men are affected
- (…)% of non-hispanic white women are affected
- (…)% of black/mexican-american women are affected
- (…)% of elderly with iron deficiency anemia get GI cancer diagnosis
- anemia
- 50%
- 2-5%
- blood loss
- pregnancy
- developing countries and impoverished areas
- 2%
- 9-12%
- 20%
- 10%
Where is iron stored?
- hemoglobin + myoglobin (disproportionate exercise/activity intolerance seen in anemia)
- macrophages of bone marrow and spleen
- liver
- transferrin in plasma
Pertaining to the flow of iron:
- You lose 1-2 mg/day through (…) and (…) in women
- Average daily diet contains (…); you cannot create iron, you have to consume it
- Iron is absorded in the (…); absorptive cells store iron in (…); stored iron is complexed with (…) and can travel system wide; (…) is taken up by erythrocyte precursors and the iron is incorporated into the RBC
- mucosal sloughing (GI) and menstruation
- 20 mg/day
- duodenum; ferritin; transferrin; transferrin
What can these lead to:
- blood loss (trauma, GI losses, menstruation)
- PUD: NSAIDs, H. pylori (acidity can affect iron absorption, bisphosphonates, chemotherapy)
- lack of iron in the diet (vegetarians/starvation)
- inability to absorb iron
- pregnancy
iron deficiency anemia
Inability to absorb iron is common with (…) or (…)
- intestinal surgery (gastric bypass)
- intestinal diseases (Crohn’s/Celiac disease: proximal intestine)
What are the risk factors associated with iron-deficiency anemia?
blood loss
- GI tract
- menstruating women
- frequent blood donation (depletes iron states)
decreased iron during reproduction and growth
- low birth weight or premature babies
- infants and children
- pregnancy and lactation
inadequate iron intake
- vegetarian diet (lack of meat increases risk if iron is not consumed from another source)
What is the most common site of blood loss for men and non-menstruating women?
GI tract
What are the clinical manifestations of iron-deficiency anemia?
- fatigue, weakness, SOB
- pale earlobes, palms, conjuctivae
- brittle, thin, coarsely ridged, and spoon-shaped (concave or koilonchia) nails
- red, sore, painful tongue (glossitis)
- angular stomatitis: dryness and soreness in the corners of the mouth
- become symptomatic: when Hgb 7 to 8 g/dl (lost about half their blood volume)
- pica
- dysphagia
What is this showing?
koilonychia
- What is the hallmark sign of iron-deficiency anemia because it is unique to this type?
- This includes cravings for certain non-nutritional substances such as what?
- pica
- ice (pagophagia), clay (geophagia), starch (amyophagia)
What clinical manifestation of iron deficiency anemia is rare and most frequently affects elderly women due to esophageal stricture?
dysphagia (trouble swallowing)
What will a CBC show for microcytic-hypochromic anemias?
- low Hgb/Hct
- low MCV/MCHC
- elevated platelets (not always)
- normal/elevated WBC count
What will a peripheral blood smear show for microcytic-hypochromic anemias?
- initially no changes
- microcytic, hypochromic RBCs
- anisocytosis, poikilocytosis
- increased platelets
- no presence of target cells
- no intra-erythrocytic crystals
What will the levels of serum iron, TIBC, serum ferritin, and transferrin be in microcytic-hypochromic anemias?
- low (<30) serum iron
- elevated TIBC
- low (<20 reliably indicated IDA) serum ferritin (normal levels may be seen in pts with hepatitis, chronic disorders)
- low (<15%) transferrin (Hgb electrophoresis, measurement of Hgb A2 and fetal Hgb)
What imaging may you need to do for microcytic-hypochromic anemias?
may need CT scan of abdomen/pelvis, uterine US, possibly colonoscopy
What special tests may you need to do when doing a microcytic-hypochromic anemia work-up?
- stool testing (make sure to do this)
- incubated fragility testing
- measurement of lead in tissue
- bone marrow aspiration
Lead causes RBCs to be (…) to testing because they are less likely to (…); this can be a way to differentiate between an underlying (…)
- resilient
- lyse
- iron deficiency
What is this describing:
- measures RBC resistance to destruction when exposed to different levels of saline solutions
- lead causes RBCs to be resilient to testing as they are less likely to lyse (differentiates b/w underlying iron deficiency)
incubated osmotic fragility testing
What are the treatment principles of iron-deficiency anemia?
- identify/eliminate sources of blood loss
- iron replacement therapy (oral preferred ROA: includes ferrous sulfate, ferrous gluconate, ferrous fumarate)
- sodium ferric gluconate complex in sucrose and iron sucrose injection
- duration of therapy: usually 6-12 months after bleeding has stopped by may continue for as long as 24 months
- Treatment of iron-deficiency anemia depends on (…) and (…)
- You should always work up for (…)
- What does treatment include?
- Why do you do slow titrated dosing?
- cause and severity
- occult blood
- oral iron: ferrous sulfate 150-325 mg po tid in slowly titrated dosing
- can cause constipation
- Oral iron (ferrous sulfate) is best absorbed on an (…) but often not tolerated due to the main side effects being (…)
- What helps the body absorb iron (and dosage)?
- What is a possibly less toxic, better tolerated drug for iron-deficiency treatment and dosage?
- After treatment, H&H can normalize in (…) months, but pts need to continue up to (…) months to replenish stores measured by ferritin
- After treatment, reticulocytes will bump up in (…) days
- What can be taken during pregnancy and lactation to help with iron-deficiency anemia?
- empty stomach; epigastric discomfort, nausea, diarrhea or constipation)
- Vitamin C: 500 mg pd
- sodium ferrous gluconate (300 mg po bid/tid) or ferrous fumarate (325 mg po bid/tid)
- 2 months, 6 months
- 1-2 days
- iron supplementation
Besides medications, what can help treat iron-deficiency anemia?
- diet: red meat, lentils, spinach, dried fruits
- blood transfusions: severe disease
- surgery: stops any underlying bleeding
Parenteral methods are effective in treating iron-deficiency anemias in which situations?
- primary blood loss is uncontrollable
- iron cannot be absorbed owing to severe malabsorption
- oral iron is not tolerated despite concerted efforts to minimize side effects (total dose and frequency of dosing depends on etiology and severity of iron loss)
- This parenteral drug is usually given after failed oral iron replacement therapy
- This parenteral drug is most commonly used in most settings outside of chronic kidney disease (and dose)
- This parenteral drug is used most commonly in settings of chronic kidney disease (usually have ACD and iron issues)
- IV ferric carboxymaltose (injectafer)
- IV ferric gluconate (ferrlecit)
- IV ferric sucrose (venofer)
What is image B demonstrating?
iron deficiency anemia
What is this describing:
- makes up a group of disorders characterized by anemia
- is caused by a defect in the mitochondrial heme synthesis (iron isn’t the problem) causing ineffective iron uptake and results in dysfunctional hemoglobin synthesis
sideroblastic anemia
In sideroblastic anemia, (…) in the bone marrow are diagnostic
ringed sideroblasts
What are erythroblasts that contain iron granules that have not been synthesized into hemoglobin?
sideroblasts
What is image K showing (what disease)?
sideroblastic anemia
What are the different types of sideroblastic anemia?
- acquired vs hereditary
- reversible sideroblastic anemia (associated with alcoholism)
- myelodysplastic syndrome (bone marrow becomes dysfunctional)
What are the clinical manifestations of sideroblastic anemia?
- iron overload (hemochromatosis)
- enlarged spleen and liver (splenomegaly/hepatomegaly)
- What is the diagnostic test for sideroblastic anemia?
- What is shown with this test?
- bone marrow examination
- dimorphism (normocytic and normochromic cells concomitantly observed with microcytic-hypochromic cells)
- Sideroblastic anemia can be (…) with decreased Hgb synthesis causing iron accumulation, especially in the mitochondria
- (…) is the most common cause of this
- It can also be caused by (…) and (…)
- acquired
- lead toxicity
- chronic alcoholism and myelodysplasia
- What are the lab values of acquired sideroblastic anemia (Hct, MCV, peripheral smear)
- Lead levels, in lead poisoning, may have (…) of red cells
- (..) can be done in diagnosis remains unknown which may show (…)
- Hct low, MCV vairs, peripheral smear with normal and hypochromic cells
- basophilic stippling
- bone marrow biopsy, ringed sideroblasts
What is this showing?
basophilic stippling (lead poisoning)
What is this showing?
ringed sideroblasts (bone marrow biopsy)
What is the treatment for acquired sideroblastic anemia?
chelation a mainstay of treatment (identify causative agent) - binds to heavy metals to remove them from the body
What are some other treatments for sideroblastic anemia?
- transfusion
- iron-depletion therapy
- phlebotomy
- prolonged erythropoietin administration
- What is the treatment for hereditary siderobastic anemia?
- Congenital sideroblastic anemia?
- Myelodysplastic syndrome?
- pyridoxine therapy (B6); life-long maintenance therapy at a lowered dose
- stem cell transplantation
- recombinant erythropoietin
- What describes a mild-to-moderate anemia due to decreased erythropoiesis?
- What conditions can lead to this?
- ACD
- AIDS, malaria, RA, lupus, hepatitis, renal failure, malignancies
What is probably the most common cause of ACD?
renal failure
What are the 4 pathologic mechanisms of why ACD happens?
- decreased erythrocyte lifespan
- suppressed production of EPO
- ineffective bone marrow response to EPO
- altered iron metabolism
- In ACD, altered iron homeostasis is due to (…) uptake and retention of iron in the cells of (…) system
- There is an increase in (…), which regulates entry of iron into circulation, decreasing duodenal iron absorption and blocks iron release from (…)
- This leads to competitive iron binding from increased (…) and (…) which doesn’t allow iron to release to make RBCs
- During inflammation, (…) release lactoferrin to bind iron and reduce its availability for bacteria
- (…) has a higher affinity for iron results, and available iron is affected in a similar manner
- increased; reticuloendothelial system (RES)
- hepcidin; RES
- lactoferrin and apoferritin
- neutrophils
- apoferritin
What is the most common microcytic-hypochromic anemia and is often first noticed in hospitalized patients secondary to an underlying disease?
ACD
Regarding ACD due to renal insufficiency:
- may have (…), an increase in nitrogenous products
- RBCs may be (…) or (…)
- diseased kidneys unable to secrete adequate amts of (…)
- uremic pts tend to hemorrhage due to defect in (…) production
- poor nutrition can lead to (…) deficiency
- chronic GI bleeding leads to (…) deficiency
- What does treatment consist of?
- uremia
- microcytic or normocytic
- EPO
- platelet production
- folic acid deficiency
- iron deficiency
- must revere renal failure; administer EPO (erythrocyte stimulating agent)
Regarding ACD due to aging:
- pts will have a gradual fall in (…) and (…) levels
- if values fall below (…) of normal have significant increased morbidity and mortality
- with age, theres an increase in (…), (…), (…), and (…) which all suppress RBC production
- What should you always evaluate anemia for?
- Hgb and Hct
- 2 SD
- chronic diseases, CA, renal diseases, and chronic inflammatory disorders
- underlying disorders
What are the 3 differentials for ACD?
- kidney disease
- aging
- chronic inflammation
Regarding ACD due to chronic inflammation:
- predominance in which individuals
- prevalence?
- 1/3 of elderly adults with anemia have (…) or (…) or both
- males > 86 yo
- 8-44%
- ACD or anemia of chronic renal failure
What are the risk factors associated with ACD?
- chronic inflammatory conditions like AI disorders (RA, SLE, vasculitis, sarcoidosis, IBD)
- cancer (both hematologic and solid tumors)
- CKD
- chronic liver disease, chronic alcoholism (check LFTs!)
- infection (acute/chronic - viral, bacterial, fungal, parasitic)
- chronic rejection after solid-organ transplant
- When working up an individual with ACD, you should obtain a detailed (…)
- Diagnosis is primarily one of (…)
- Best way to diagnose is to document an anemia of underproduction in the setting of a (…) usually (…) illness
- history and physical exam
- exclusion
- systemic, inflammatory
What laboratory tests can you obtain for diagnosing ACD?
- CBC, retic count, retic index
- peripheral smear
- serum iron, TIBC, transferrin saturation, ferritin
- EPO level
- bone marrow not usually done but may be eventually necessary to rule out malignancy or infection
What are the usual lab results for ACD:
- Hgb
- retic count
- serum iron
- transferrin saturation
- serum ferritin
- peripheral smear
- bone marrow
- Hgb: 8-9.5 g/dL
- retic count: low
- serum iron: low
- transferrin saturation: low
- serum ferritin: normal or increased (iron storage and APR)
- peripheral smear: hypochromic normocytic RBCs; will become macrocytic
- bone marrow: normal erythmoid precursors (true exclusion)
- What hgb levels do you transfuse everyone?
- What about pts with cardiac disease?
- below 7
- below 8
- What is the main treatment of ACD?
- What is the treatment for acute general Rx?
- treat the underlying disease or disorder
- transfusion reserved for severe anemia, especially if complicated with ongoing bleeding
What are different eryhtropoiesis stimulating agents?
- procrit
- aranesp
Regardind chronic treatment of ACD:
- ESAs are FDA approved for treating anemia from (…)
- ESA is dose (…), with lowest sufficient dose; Hgb target (…) widely accepting
- High ESA dose in CKD is associated with an increase of (…) and (…) events
- ESA use in Ca patients is correlated with an increase in (…) and (…), so do not use in chemotherapy patients when treatment goal is to cure
- can use (…) but rule out deficiency before using (…); monitory (…) with ESA use; may need to consider (…) if non-responsive
- CKD, chemotherapy, ziduvidine therapy
- individualized; 10-12
- CV and thromboembolic events
- tumor progression and mortality
- supplemental iron; EPO; iron; parenteral iron
What are the main two indications for procrit and aranesp use?
- CKD
- chemotherapy
Anemia of chronic disease is caused by:
1. immunoglobulin G binding to erythrocytes at normal body temps
2. autoantibodies against erythrocyte surface antigens
3. reduced response to erythropoietin
4. paroxysmal nocturnal hemoglobinuria
- reduced response to erythropoietin
others: - WAIHA
- AIHA
- congential/acquired
All of the following are suggestive of iron deficiency anemia except:
a. koilonychia
b. pica
c. decreased serum ferritin
d. decreased total iron-binding capacity
e. low reticulocyte count
D. decreased TIBC
TIBC will be increased
